Why Monkeypox Vaccine Shortage May Threaten the Immunocompromised

Monkeypox vaccine dose shortages in the United States, which are expected to last for months, are raising immediate questions about how well and for how long a shot can protect against the virus.

The vaccine, called Geneos, is approved as a two-dose regimen, but most people at risk of infection are getting a single dose — if they can find it. Now the shortage has prompted federal officials to consider a rarely used approach: a so-called dose-deferring strategy, which delivers shots that each contain only one-fifth of a dose.

For most recipients, a single shot should be enough to ward off severe disease, and there is some evidence that even smaller doses may be effective. But early research suggests that people with HIV or other conditions that weaken the immune system may be less protected than those who do not have such diseases, according to some experts.

“One dose is better than none,” said Dr. Alexandra Yonts, an infectious disease physician at Children’s National Hospital in Washington, DC, but “people with HIV and other immunocompromised individuals need to be aware that they have adequate levels.” may not be protected from infection, even with vaccination,” she said.

Even two weeks after the shot, when the antibody response is ongoing, immunocompromised people “may still need to use all other precautions, in accordance with public health guidance,” she said.

The findings also suggest that some men should be preferred for full vaccination. This may be difficult given the lack of supply.

Federal officials have ordered about seven million doses of Jynneos, but the shots won’t arrive for months. So far, the Biden administration has shipped about 600,000 doses to the states. It said last week that 800,000 additional doses were being allocated to states, but distribution could take weeks.

Facing shortages, some cities, including Washington and New York, are restricting second doses to increase their supplies. Food and Drug Administration and CDC officials disagree with that strategy, noting that Zynos is approved as a vaccine to be given in two doses spaced 28 days apart.

But as federal health officials declared a public health emergency on Thursday, FDA Commissioner Dr. Robert Califf said the agency is now looking at authorizing shots that contain only one-fifth of the regular dose, which penetrate the layers of the skin. is given between Under it.

The FDA would be required to grant Jynneos an emergency use authorization to be administered in this manner.

When supplies of other vaccines are in short supply a dose reduction approach is used. But giving intradermal shots requires more skill than is required by more traditional vaccinations.

One shot is probably enough to prevent severe symptoms in most people, and dosage avoidance strategies may work as well. But it’s not clear whether a scaled-back regimen is enough to prevent infection, and if so, how long that immunity might last, federal health officials said.

“We are in a data-free zone,” said Dr Emily Erbelding, an infectious disease specialist at the National Institutes of Health who oversees the testing of COVID vaccines in special populations.

An oft-cited figure says the vaccine is 85 percent effective against monkeypox. This data comes not from Genios’ trials, but from a small 1988 study that looked at the incidence of monkeypox in people who had been vaccinated for smallpox earlier in their lives.

No major clinical trials of Genos as a vaccine for monkeypox were conducted in humans prior to its approval. Instead, the FDA relied on measures of antibody responses in small groups of people after vaccination with Jynneos compared to those produced by the earlier vaccine for smallpox, ACAM2000.

In studies led by its creator, the Bavarian Nordic, two doses of Zynos elicited antibody levels in humans that were nearly identical to those following a single shot of ACAM2000.

Antibody levels initially rose for two weeks after the first shot of Jynneos and then remained flat until the second dose four weeks later, when they rose to very high levels – higher than the level recorded with the ACAM2000.

The scientists read that this means that if the first dose is not followed by a second dose, the protection may not be long-lasting.

“Ideally, a second dose would be administered if protection is desired for more than that four-week period,” Dr. Younts, who reviewed the data for the FDA as a staff scientist.

She said delaying the second dose by eight weeks may be appropriate. “But if it’s going to be like six months, I think the priority will lean more towards people who are more severely immunized,” she said.

The FDA suggested Thursday that injecting one-fifth of a regular dose of Gynos between the layers of the skin may be effective, according to limited research. The skin contains many more immune cells that react to vaccines.

But the research is very limited. NIH scientists had planned to test the dose-sparing strategy in a clinical trial beginning in a few weeks. It is not clear whether those plans will be postponed or accelerated.

There was already little information about the performance of GENEOS in people living with HIV, especially those with severe immune problems. In a study by Bavarian Nordic, the antibody response to vaccination decreased: 28 days after the first shot, 67 percent of people with HIV produced antibodies, compared to 84 percent of uninfected people.

While Dr Yonts said the data from that trial was not conclusive, a reduced antibody response is often seen in immunocompromised people given other vaccines. For example, when evaluating COVID vaccines, researchers found that HIV patients were more likely to have a breakthrough infection.

“Individuals with severe or moderate immune suppression are recommended for additional doses of common vaccines,” said Kerry Althoff, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health who led the COVID Vaccine Study. increases, the response to vaccines decreases.”

The CDC and the New York City Department of Health state that Zineos is safe for people with HIV, but agencies have not addressed its effectiveness in that population.

Conversely, health officials in the UK say the vaccine may not protect you as well if you are “HIV positive or have any other condition or treatment that leads to a weakened immune system.”

The vaccine’s package insert also notes that immunocompromised people “may have a reduced immune response.”

“Two shots could be very important in this population, which is something that is not really happening in the public health response,” said Dr., an infectious disease physician at Queen Mary University of London. Chloe Orkin, referring to immunocompromised people.

But until higher doses become available, state and local health departments may have no choice but to stick with scaled-back regimens.

“In an environment of scarcity, we have to do everything possible to get the benefits of the vaccine in the city as quickly as possible,” said Patrick Gallahue, a spokesman for the New York City Department of Health.